Charalampos Siristatidis

Controlled ovarian hyperstimulation for IVF: impact on ovarian, endometrial and cervical cancer—a systematic review and meta-analysis

BACKGROUND In response to the ongoing debate on the long-term effects of assisted reproduction technologies, such as IVF, we systematically reviewed and meta-analyzed available evidence on the association between controlled ovarian hyperstimulation for IVF and risk of ovarian, endometrial and cervical cancer. METHODS Eligible studies were identified and pooled effect estimates for relative risk (RR) were calculated by cancer type among two reference groups (general population or infertile women), through fixed- or random-effects models as appropriate. RESULTS Nine cohort studies were synthesized, corresponding to a total size of 109 969 women exposed to IVF, among whom 76 incident cases of ovarian, 18 of endometrial and 207 cases of cervical cancer were studied. The synthesis of studies with general population as the reference group pointed to a statistically significant positive association between IVF and increased risk for ovarian (RR = 1.50, 95% confidence interval (CI): 1.17-1.92) and endometrial (RR = 2.04, 95% CI: 1.22-3.43), but not cervical (RR = 0.86, 95% CI: 0.49-1.49) cancers. On the contrary, when infertile women were used as the reference group, no significant associations with ovarian, endometrial or cervical cancer types were noted (RR = 1.26, 95% CI: 0.62-2.55 RR = 0.45, 95% CI: 0.18-1.14 and RR = 5.70, 95% CI: 0.28-117.20, respectively). CONCLUSIONS IVF does not seem to be associated with elevated cervical cancer risk, nor with ovarian or endometrial cancer when the confounding effect of infertility was neutralized in studies allowing such comparisons. Of note, only one study provided follow-up longer than 10 years for the group exposed to IVF. Future cohort studies should preferably use infertile women as the reference group, rely on IVF-registered valid exposure data, adjust for a variety of meaningful confounders and adopt relatively longer follow-up periods before sound conclusions are drawn.

Mediators of chronic inflammation in polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) is an endocrine disorder affecting 5–10% of reproductive-age women. Hyperandrogenemia, which characterizes the syndrome, stimulates the maturation of adipocytes and favors central obesity. The linking hub between obesity and other metabolic manifestations of the syndrome seems to be chronic low-grade inflammation. We discuss the most reliable current data regarding the role of inflammatory mediators in PCOS, with particular focus on the genetic mechanisms implicated. C-reactive protein levels are 96% higher in PCOS patients than in healthy controls. Patients with the -308A polymorphism of the tumor necrosis factor-α gene have elevated androgens in comparison with carriers of the -308G. Interleukin 18 (IL-18) is elevated in lean patients, with a further rise in the presence of obesity and insulin resistance. Polymorphisms of the IL-1a, IL-1b and IL-6 genes have also been associated with PCOS. Plasminogen activator inhibitor-1 levels are positively associated with the syndrome, and carriers of the 4G allele of the 4G/5G polymorphism are at risk of developing PCOS. Other mediators discussed include adhesion molecules, osteoprotegerin, asymmetric dimethylarginine, homocysteine and advanced glycation end-products. The elucidation of the pathogenetic mechanisms implicated in PCOS and their connection with low-grade inflammation may in the future offer the opportunity for the formulation of novel therapeutic strategies and individualized therapy for these patients.

In Vitro Maturation in Women with vs. without Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis.

Objective To evaluate in vitro maturation (IVM) in sub-fertile women with polycystic ovarian syndrome (PCOS) undergoing in vitro fertilisation (IVF), by comparing outcomes with a control group of non-PCOS. Study design A search strategy was developed for PubMed and studies reporting rates of the following outcomes (live birth; clinical pregnancy; implantation; cycle cancellation; oocyte maturation; oocyte fertilization; miscarriage) between patients with PCOS, PCO and controls undergoing IVM were deemed eligible. The review was conducted in accordance to the PRISMA guidelines and included studies quality was assessed through the Newcastle-Ottawa Quality scale. ORs with their corresponding 95% CIs were calculated for the main analysis and subgroup analyses were performed for PCOS cases vs. controls and PCOS vs. PCO cases. Alternative analyses were performed for live birth and clinical pregnancy, based on cycles and on women. Subgroup analyses for FSH stimulation, hCG priming and type of procedure (IVF/ICSI) were undertaken for all meta-analyses encompassing at least four study arms. Random effects models were used to calculate pooled effect estimates. Results Eleven studies were identified. A total of 268 PCOS patients (328 cycles), 100 PCO patients (110 cycles) and 440 controls (480 cycles) were included in the meta-analysis. A borderline trend towards higher birth rates among PCOS patients emerged (pooled OR = 1.74, 95%CI: 0.99–3.04) mainly reflected at the subgroup analysis vs. controls. Clinical pregnancy (pooled OR = 2.37, 95%CI: 1.53–3.68) and implantation rates (pooled OR = 1.73, 95%CI: 1.06–2.81) were higher, while cancellation rates lower (pooled OR = 0.18, 95%CI: 0.06-0.47) among PCOS vs. non-PCOS subjects; maturation and miscarriage rates did not differ between groups, while a borderline trend towards lower fertilization rates among PCOS patients was observed. Conclusion The present meta-analysis provides preliminary evidence on the effectiveness of IVM as a treatment option when offered in sub-fertile PCOS women, as the latter present at least as high outcome rates as those in non-PCOS.

Potential Pathophysiological Mechanisms of the Beneficial Role of Endometrial Injury in In Vitro Fertilization Outcome.

Successful embryo implantation is a complex process that involves multiple biological mechanisms and reciprocal interactions between the embryo and the proliferated endometrium. In this review, we provide an informative contribution on the pathways underlying the beneficial nature of endometrial injury toward improving implantation rates of embryos conceived and through in vitro fertilization. The evidence published to date are in favor of inducing local endometrial injury in the preceding cycle of ovarian stimulation to improve pregnancy outcomes in women with unexplained and recurrent implantation failure. Endometrial injury triggers a series of biological responses but the findings suggest that no particular pathway is solely adequate to explain the association between trauma and improved pregnancy rates rather than a cluster of events in response to trauma which benefits embryo implantation in ways both known and unknown to the scientific community.

Clinical complications after transvaginal oocyte retrieval: A retrospective analysis

There are little systematic data reported in the literature on complications observed after transvaginal oocyte retrieval (OR) guided by ultrasound. We report our experience in 542 in vitro fertilisation cycles. The frequency of severe complications in our patients was 0.72%; of these, two cases were bronchospasm during anaesthesia (0.36%) and two were cases of intraperitoneal bleeding (0.36%); minor vaginal bleeding was the most frequent complication (18.08%), which was treated easily. Through this retrospective analysis, it is evident that clinical suspicion is of particular importance in detecting post-OR complications on one hand, but on the other these complications are rare and most are treated conservatively.

Artificial Intelligence in IVF: A Need

Predicting the outcome of in-vitro fertilization (IVF) treatment is an extremely semantic issue in reproductive medicine. Discrepancies in results among reproductive centres still exist making the construction of new systems capable to foresee the desired outcome a necessity. As such, artificial neural networks (ANNs) represent a combination of a learning, self-adapting, and predicting machine. In this review hypothesis paper we summarize the past efforts of the ANNs systems to predict IVF outcomes. This will be considered together with other statistical models, such as the ensemble techniques, Classification And Regression Tree (CART) and regression analysis techniques, discriminant analysis, and case based reasoning systems. We also summarize the various inputs that have been employed as parameters in these studies to predict the IVF outcome. Finally, we report our attempt to construct a new ANN architecture based on the Learning Vector Quantizer promising good generalization: a system filled by a complete data set of our IVF unit, formulated parameters most commonly used in similar studies, trained by a network expert, and evaluated in terms of predictive power.

Bakri balloon tamponade for the management of postpartum hemorrhage.

Maternal mortality –0.46 (0.004) –0.36 (0.063) West: –0.63 (0.008) West: –0.69 (0.013) East: –0.24 (0.478) East: 0.04 (0.919) Central: 0.75 (0.246) Central: 0.99 (0.037) Southern: –0.80 (0.101) Southern: –0.67 (0.327) Neonatal mortality –0.39 (0.019) –0.30 (0.119) West: –0.55 (0.027) West: –0.53 (0.079) East: –0.04 (0.912) East: –0.24 (0.539) Central: –0.92 (0.080) Central: –0.98 (0.116) Southern: –0.52 (0.369) Southern: –0.23 (0.773) Early neonatal mortality –0.31 (0.062) –0.22 (0.254) West: –0.47 (0.064) West: –0.44 (0.156) East: –0.08 (0.803) East: –0.26 (0.496) Central: –0.96 (0.034) Central: –0.97 (0.154) Southern: –0.49 (0.401) Southern: –0.18 (0.820) Late neonatal mortality b –0.47 (0.004) –0.39 (0.043) West: –0.59 (0.014) West: –0.55 (0.063) East: 0.05 (0.877) East: –0.11 (0.787) Central: –0.84 (0.156) Central: –0.99 (0.056) Southern: –0.59 (0.295) Southern: –0.37 (0.627)

A short narrative review of the feasibility of adopting mild ovarian stimulation for IVF as the current standard of care

IntroductionMild ovarian stimulation has been conceived, proposed and implemented in clinical practice as a safer and cheaper alternative to conventional strategies of controlled ovarian hyperstimulation in preparation for in vitro fertilization (IVF). Our aim was to summarize the key evidence on this topic and explore its possible role as the standard treatment option for women undergoing IVF.Materials and MethodsA short narrative review of the existing literature, with emphasis on mild ovarian stimulation clinical and cost effectiveness, as well as treatment limitations.ResultsNumerous studies highlight mild ovarian stimulation’s favorable characteristics with respect to oocyte/embryo quality, reduced patient risk, and ease of intervention. There is, however, a need for high-quality laboratory environment. Limitations regarding poor responders, older women, or those seeking ovarian stimulation for non-infertility indications should also be considered. Finally, outcomes on the cumulative success rates and the cost effectiveness of mild ovarian stimulation remain inconclusive.ConclusionMild ovarian stimulation protocols for IVF should currently be implemented only in carefully selected populations. Further research is needed to clarify the remaining controversies in this IVF approach.

Feasibility of office hysteroscopy through the “see and treat technique” in private practice: a prospective observational study

PurposeThe purpose of the study was to examine the feasibility of office hysteroscopy through the no-touch “see and treat technique” in a routine basis in private practice.MethodsIn the private practice of two trained gynecologists, women with an indication for further investigation of the uterine cavity were treated with the technique. A total of 112 consecutive women were prospectively allocated to a “no-touch” and “see and treat” technique of hysteroscopy. Neither anaesthesia nor analgesia was used as soon as criteria were met. Hysteroscopy was performed using a rigid 3.4-mm hysteroscope and a medium of 0.9% saline.ResultsTreatment efficacy and patient compliance were evaluated through scores on a visual analogue scale (VAS) for pain, complications and success rates, along with the symphony between hysteroscopic findings and histology. The patients’ pain score on the VAS was low and only in 2 out of 112 cases there was a marked discomfort. In four cases suggested treatment was not successful, because of the fear of the patient. In 60.71% of cases that hysteroscopy was indicated, the uterine cavity was normal. No complications or adverse effects were noted. Apart from one case, there was a full agreement between hysteroscopic findings and histology.ConclusionOffice hysteroscopy is a successful and well-tolerated procedure. Through adequate expertise it should be considered the method of choice in private basis, at the same time when exploration of the uterine cavity is needed.

Effect of maternal obesity on pregnancy outcomes and long-term metabolic consequences.

Recent years have witnessed a worldwide increase in the prevalence of pre-pregnancy maternal obesity. A survey carried out in the USA between 2003 and 2006 reported that 32% of women aged 20-44 years were classified as obese (WHO 2009).1 The rise in obesity among pregnant women goes hand in hand with the upward trend of obesity in the general population. In addition, the percentage of women gaining excessive weight during pregnancy has also increased.2,3